Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in patients who have compromised immune systems. Examples of LPDs include, but are not limited to, follicular lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, hairy cell leukemia, lymphomas, multiple myeloma, Waldenstrom's macroglobulinemia, Wiskott-Aldrich syndrome, post-transplant lymphoproliferative disorder, autoimmune lymphoproliferatieve syndrome (ALPS), lymphoid interstitial pneumonia, and CD30-positive lymphoproliferative disorders. Examples of CD30-positive lymphoproliferative disorders include lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma.
Lymphomatoid papulosis (LYP) is characterized by multiple papules and nodules, which regress spontaneously. Three histologic subtypes have been described, which represent a spectrum with overlapping features and do not carry prognostic significance. Type A lesions have a few tumor cells in a background of inflammatory cells including neutrophils, eosinophils, and histiocytes. Type B lesions are characterized by epidermotropic lymphocytes with cerebriform nuclei mimicking mycosis fungoides. Type C lesions have sheets of large atypical lymphoid cells with only a few admixed inflammatory cells. The large atypical lymphoid cells are thought to be of T cell origin. Various histologic types may be present in individual patients at the same time. In LYP types A and C the large atypical cells express CD30, CD3, and CD4. CD2 and CD5 are usually expressed. These cells also express the cytotoxic markers TIA-1 and granzyme. The large atypical cells do not express CD8, CD7, or CD56. The cells may lose expression of CD3. In LYP type B the atypical cells are usually CD30 negative. Five year survival rates for LYP are 100%; however up to 20% of patients develop LYP-associated malignant lymphomas (e.g., mycosis fungoides, Hodgkin lymphoma, systemic or cutaneous CD30+ large T-cell lymphoma), which result in a fatal outcome of 2% of patients.
Primary cutaneous anaplastic large cell lymphoma (ALCL) is composed of large atypical to anaplastic appearing lymphoid cells. This disease mainly affects adults with a peak in the sixth decade, but cases have been reported in children. It usually presents as a solitary rapidly growing nodule. The skin overlying the lesion may ulcerate. Histologically the cells grow in sheets. Mitotic figures are frequent. Clusters of small reactive lymphocytes are found within and around the tumor cells. The malignant cells express CD2, CD3, CD4, CD30, and cytotoxic markers including TIA-1, granzyme, and perforin. Loss of T-cell antigen expression is not infrequent. The malignant cells do not express EMA or ALK. Five year survival rates approach 90%. Interestingly, up to 40% of C-ALCL show spontaneous regression similarly to LYP.
Improved methods for detecting, investigating, and treating CD30-positive lymphoproliferative disorders (e.g., lymphomatoid papulosis; primary cutaneous anaplastic large cell lymphoma) are needed.